TanshinoneⅡA attenuates carotid artery atherosclerosis by deactivating mast cells in adventitia
10.3760/cma.j.issn.0253-3758.2019.08.008
- VernacularTitle: 丹参酮ⅡA抑制血管外膜肥大细胞活化减轻颈动脉粥样硬化斑块形成
- Author:
Weiliang SUN
1
;
Jing GUO
1
;
Zhuo CHEN
2
;
Lin PAN
1
;
Jingang ZHENG
3
;
Yanxiang GAO
3
Author Information
1. Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100029, China
2. Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
3. Department of Cardiology, China-Japan Friendship Hospital, Beijing 100029, China
- Publication Type:Journal Article
- Keywords:
Atherosclerosis;
Carotid artery;
Mast cells;
Salvia miltiorrhiza
- From:
Chinese Journal of Cardiology
2019;47(8):634-639
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of tanshinone ⅡA on atherosclerosis plaque formation and adventitial mast cells activation in high-fat-diet induced Apo E-/- mice model.
Methods:Sixteen 8-week-old Apo E-/-male mice and eight 8-week-old C57BL/6 male mice were randomly allocated into following group: the control group (C57BL/6 + carboxymethyl cellulose per gavage), the atherogenic group (Apo E-/-+carboxymethyl cellulose per gavage) and the tanshinoneⅡA intervention group (Apo E-/-+30 mg/kg tanshinone ⅡA per gavage). All three groups were fed with high-fat-diet for 26 weeks. Tanshinone ⅡA/carboxymethyl cellulose was applied by the method of gavage administration 6 weeks before execution. After 26 weeks, tumor necrosis factor-α (TNF-α) andinterleukin (IL)-6 levels in serum were assessed by ELISA. Carotid artery was removed, fixed with paraformaldehyde, embedded with paraffin and sectioned. Percentage of stenosis was evaluated on HE stained sections. Plaque progression was assessed by Movat staining. Toluidine blue staining was used to evaluate mast cells infiltration and activation. Immunochemistry staining was used to assess 5-HT, TNF-α and IL-6 expression. mRNA expression of mast cell marker Fcer1a in adventitial tissue was detected by real time-PCR.
Results:After high-fat-diet for 26 weeks, the mice in the atherogenic group showed advanced atherosclerosis, tanshinoneⅡA intervention reduced the percentage of carotid artery stenosis caused by atherosclerotic plaque formation ((58.48±8.07)% vs. (80.31±4.08)%, P<0.05). Compared with the atherogenic group, tanshinone ⅡA intervention group had lower level of TNF-α ((12.39±1.62)pg/ml vs. (17.44±1.42)pg/ml) and IL-6 ((116.24±12.16)pg/ml vs. (166.05±19.09)pg/ml) in serum, lower TNF-α ((20 145±1 556) vs. (25 288±1 671)) and IL-6 ((25 688±1 604) vs. (35 286±4 198)) expression in adventitia (all P<0.05). TanshinoneⅡA intervention also decreased the number of mast cells infiltration and activation, reduced 5-HT expression and mast cell marker Fcer1a mRNA relative expression in adventitia (all P<0.05).
Conclusions:Tanshinone ⅡA could attenuate induced by high-fat-diet carotid artery atherosclerosis in Apo E-/- mice. The protective effect of tanshinoneⅡA is probably mediated through reducing the number and activation percentage of mast cells, decreasing the release of inflammatory cytokines and inflammation of carotid artery in adventitia.
